Title: A nematode kinesin required for cleavage furrow advancement
Abstract: Dividing cells need to coordinate the separation of chromosomes with the formation of a cleavage plane. There is evidence that microtubule bundles in the interzone region of the anaphase spindle somehow control both the location and the assembly of the cleavage furrow [1Cao LG Wang YL Signals from the spindle midzone are required for the stimulation of cytokinesis in cultured epithelial cells.Mol Biol Cell. 1996; 7: 225-232Crossref PubMed Scopus (160) Google Scholar, 2Wheatley SP Wang Y Midzone microtubule bundles are continuously required for cytokinesis in cultured epithelial cells.J Cell Biol. 1996; 135: 981-989Crossref PubMed Scopus (186) Google Scholar, 3Williams BC Riedy MF Williams EV Gatti M Goldberg ML The Drosophila kinesin-like protein KLP3A is a midbody component required for central spindle assembly and initiation of cytokinesis.J Cell Biol. 1995; 129: 709-723Crossref PubMed Scopus (150) Google Scholar]. A microtubule motor that concentrates in the interzone, MKLP1, has previously been implicated in the assembly of both the metaphase spindle and the cleavage furrow [4Wright BD Terasaki M Scholey JM Roles of kinesin and kinesin-like proteins in sea urchin embryonic cell division: evaluation using antibody microinjection.J Cell Biol. 1993; 123: 681-689Crossref PubMed Scopus (67) Google Scholar, 5Nislow C Sellitto C Kuriyama R McIntosh JR A monoclonal antibody to a mitotic microtubule-associated protein blocks mitotic progression.J Cell Biol. 1990; 111: 511-522Crossref PubMed Scopus (81) Google Scholar, 6Adams RR Tavares AA Salzberg A Bellen HJ Glover DM pavarotti encodes a kinesin-like protein required to organize the central spindle and contractile ring for cytokinesis.Genes Dev. 1998; 12: 1483-1494Crossref PubMed Scopus (298) Google Scholar]. To gain insight into mechanisms that might underlie interdependence of the spindle and the cleavage furrow, we used RNA-mediated interference (RNAi) to study the effects of eliminating MKLP1 from Caenorhabditis elegans embryos. Surprisingly, in MKLP1(RNAi) embryos, spindle formation appears normal until late anaphase. Microtubule bundles form in the spindle interzone and the cleavage furrow assembles; anaphase and cleavage furrow ingression initially appear normal. The interzone bundles do not gather into a stable midbody, however, and furrow contraction always fails before complete closure. This sequence of relatively normal mitosis and a late failure of cytokinesis continues for many cell cycles. These and additional results suggest that the interzone microtubule bundles need MKLP1 to encourage the advance and stable closure of the cleavage furrow.